Prevention investigators in our Center and elsewhere have demonstrated that drug abuse prevention efficacy can be significantly enhanced by targeting individuals who are most vulnerable to developing problems and tailoring message content and format based on the characteristics of these individuals. Further development of laboratory models to identify individuals who are vulnerable to developing regular and problematic patterns of drug use and identifying the characteristics of these individuals that predispose them to vulnerability and/or influence the efficacy of communication/education programs is of critical importance for informing and advancing the field of drug abuse prevention. This application proposes five years of research to continue laboratory investigations of individual differences associated with drug abuse vulnerability. Prior epidemiological research has established a link between the biologically-based personality trait of sensation-seeking (or novelty-seeking) and drug abuse in humans. Research with rat models suggests that novelty-seeking behavior is predictive of individual differences in dopamine function and in the reinforcing and other behavioral effects of drugs of abuse. Our recent clinical laboratory studies demonstrate an association between sensation seeking and individual differences in both brain function and in the reinforcing and other behavioral effects of drugs of abuse. Sensation seeking consists of dissociable biologically-based dimensions of reward seeking and inhibition; each of these dimensions has been postulated to play an important role in determining drug abuse vulnerability via distinct and separable biobehavioral mechanisms. A multidisciplimary approach combining laboratory abuse liability assessment and brain imaging methodologies will be used to examine the separate and combined effects of reward seeking and inhibition traits on 1) drug abuse vulnerability, 2) brain responses associatedwith reward and inhibition processing, 3) brain responses associated with drug effects on reward and inhibition processing, and 4) brain responses to emotional and novel stimulus materials. These studies will support the development of more efficacious prevention interventions by defining individual characteristics and associated brain processes that are linked to drug abuse vulnerability that can be used to improve the precision of targeted and tailored programs.